PRODE recovers essential and context-essential genes through neighborhood-informed scores

PRODE recovers essential and context-essential genes through neighborhood-informed scores

Abstract Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene eff...

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Bibliographic Details
Main Authors: Thomas Cantore, Paola Gasperini, Riccardo Bevilacqua, Yari Ciani, Sanju Sinha, Eytan Ruppin, Francesca Demichelis
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Genome Biology
Subjects:
Essentiality
Context-essentiality
Gene effect
PPI
Cancer vulnerabilities
Neighborhood-informed scores
Online Access:https://doi.org/10.1186/s13059-025-03501-0
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Summary:Abstract Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene effects with protein–protein interactions to generate neighborhood-informed essential (NIE) and neighborhood-informed context essential (NICE) scores. It outperforms the canonical gene effect approach in recovering missed essential genes in shRNA screens and prioritizing context-essential hits from CRISPR-KO screens, as supported by in vitro validations. Applied to Her2 + breast cancer tumor samples, PRODE identifies oxidative phosphorylation genes as vulnerabilities with prognostic value, highlighting new therapeutic opportunities.
ISSN:1474-760X

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